The objectives of this proposal are to examine the pharmacokinetics of nitroglycerin, in experimental animals, as functions of dose, routes of administration, drug interaction, individual metabolic activity, diet and other factors. In the coming year, the following studies are planned: 1. to examine the mechanisms which are responsible for the abnormally high systemic clearance of nitroglycerin (ca. 600 ml/min./kg in the rat and ca. 25-30 1/min. in man); 2. to investigate the kinetics of nitroglycerin (and also those of ISDN and its metabolites) in selected blood vessels; and 3. to examine the relationships between nitrate tolerance and drug/metabolites kinetics.